A diacylglycerol lipase-CB2 cannabinoid pathway regulates adult subventricular zone neurogenesis in an age-dependent manner

Mol Cell Neurosci. 2008 Aug;38(4):526-36. doi: 10.1016/j.mcn.2008.05.001. Epub 2008 May 15.


The subventricular zone (SVZ) is a major site of neurogenesis in the adult. We now show that ependymal and proliferating cells in the adult mouse SVZ express diacylglycerol lipases (DAGLs), enzymes that synthesise a CB1/CB2 cannabinoid receptor ligand. DAGL and CB2 antagonists inhibit the proliferation of cultured neural stem cells, and the proliferation of progenitor cells in young animals. Furthermore, CB2 agonists stimulate progenitor cell proliferation in vivo, with this effect being more pronounced in older animals. A similar response was seen with a fatty acid amide hydrolase (FAAH) inhibitor that limits degradation of endocannabinoids. The effects on proliferation were mirrored in changes in the number of neuroblasts migrating from the SVZ to the olfactory bulb (OB). In this context, CB2 antagonists reduced the number of newborn neurons appearing in the OB in the young adult animals while CB2 agonists stimulated this in older animals. These data identify CB2 receptor agonists and FAAH inhibitors as agents that can counteract the naturally observed decline in adult neurogenesis that is associated with ageing.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Aging / physiology*
  • Animals
  • Cell Differentiation / physiology*
  • Cell Line
  • Cells, Cultured
  • Cerebral Ventricles / cytology
  • Cerebral Ventricles / enzymology
  • Cerebral Ventricles / growth & development*
  • Female
  • Lipoprotein Lipase / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neurons / cytology
  • Neurons / enzymology
  • Neurons / physiology
  • Receptor, Cannabinoid, CB2 / physiology*
  • Signal Transduction / physiology*
  • Stem Cells / cytology
  • Stem Cells / enzymology
  • Stem Cells / physiology


  • Receptor, Cannabinoid, CB2
  • Lipoprotein Lipase